Melanin is fundamental compound in skin pigmentation, and much of the skin pigmentation observed is dependent upon the loading and retention of melanosomes in the keratinocytes. Melanin is produced by a complex set of reactions within a melanocyte involving, at a basic level, the enzyme tyrosinase and L-tyrosine as a substrate. Melanogenesis can be stimulated by paracrine factors originating from keratinocytes such as stem cell factor and endothelin-1 in response to UV stress. During melanogenesis, tyrosinase catalyzes the conversion of L-tyrosine to DOPA (L-3,4-dihydroxyphenylalanine) and of DOPA to dopaquinone. Dopaquinone undergoes further conversion to form melanin. Melanin aggregates in organelles known as the melanosomes which are transferred to keratinocytes along slender filaments of the melanocyte known as dendrites. Since there are approximately 36 keratinocytes for each melanocyte in the epidermis, the melanocytes rely on these dendritic structures to “reach” neighboring keratinocytes for melanosome transfer. Melanin carrying keratinocytes then migrate upward toward the skin surface in a constant renewal process.
There are approximately 1500 gene products expressed in a melanosome, with 600 of them being expressed at any given time, and 100 of them believed to be unique to the melanosome. In addition, there are many regulatory elements involved in signaling, in the transport of melanosomes within the melanocyte, and in the transfer of melanosomes to the keratinocytes. Some pathways are relatively well elucidated, while others are not. Identifying and better understanding the biochemical pathways involved in melanin transfer can help identify skin tone agents for regulating hyperpigmentation and melanin overproduction.
Accordingly, it would be desirable to identify skin care actives that inhibit the transfer of melanin from melanocytes to keratinocyes. It would also be desirable to formulate cosmetic compositions for improving the appearance of hyperpigmented skin that include such actives. It would further be desirable to treat skin pigmentation conditions using such compositions.